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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

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Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK Institute of Developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clea

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

Distributed Secondary Control Based on Dynamic Diffusion Algorithm for Current Sharing and Average Voltage Regulation in DC Microgrids

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 597-607页

作者： Dawei Liao Fei Gao Daniel J.Rogers Wentao Huang Dong Liu Houjun Tang Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghaiChina Department of Engineering Science University of OxfordOxford OX12JDU.K. IEEE

This paper introduces a distributed secondary control scheme for achieving current sharing and average voltage regulation objectives in a DC *** proposed scheme employs a dynamic diffusion algorithm(DDA)instead of the consensus algorithm to enable distributed communication among *** help understand DDA,the relation of DDA and other diffusion algorithms is discussed in detail and its superiority is shown by comparison with diffusion and consensus ***,considering the discrete nature and different sampling time of the digital controller and communication network,a z-domain model of the entire DC microgrid is *** influence of communication and secondary control parameters on the system stability is *** on the established model,the tolerable communication rates are ***-time simulations conducted on the OPAL-RT platform validate the effectiveness of the proposed scheme,showcasing its advantages in terms of convergence speed and stability.

关键词： Cooperative control DC microgrid diffusion algorithm discrete-time modeling distributed secondary control

The Triple Combination of Meropenem,Avibactam,and a Metallo-b-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different b-Lactamase Producers

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Engineering 2024年第7期38卷 124-132页

作者： Zhuoren Ling Alistair James Macdonald Farley Aditya Lankapalli Yanfang Zhang Shonnette Premchand-Branker Kate Cook Andrei Baran Charlotte Gray-Hammerton Claudia Orbegozo Rubio Edgars Suna Jordan Mathias Jürgen Brem Kirsty Sands Maria Nieto-Rosado Maria Mykolaivna Trush Nadira Naznin Rakhi Willames Martins Yuqing Zhou Christopher Joseph Schofield Timothy Walsh Department of Biology&Ineos oxford Institute for Antimicrobial Research University of OxfordOxford OX13REUK Chemistry Research Laboratory Department of Chemistry and the Ineos Oxford Institute for Antimicrobial ResearchUniversity of OxfordOxford OX13TAUK Latvian Institute of Organic Synthesis Riga LV-1006Latvia Department of Medical Microbiology Division of Infection and ImmunitySchool of MedicineCardiff UniversityCardiff CF144XNUK Enzymology and Applied Biocatalysis Research Center Faculty of Chemistry and Chemical EngineeringBabes-Bolyai UniversityCluj-Napoca 400028Romania

This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-blactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-b-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combination using the agar dilution *** frequency of resistance(FoR)to MEM combined with InC58 was *** were sequenced and tested for cross resistance,fitness,and the stability of the resistance *** with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-blactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-blactamase(VIM)-carrying Pseudomonas aeruginosa(***)and OXA-23-carrying Acinetobacter baumannii(***).The FoR to MEM plus InC58 ranged from 2.22×10^(-7)to 1.13×10^(-6).The resistance correlated with mutations to ompC and comR,affecting porin C and copper permeability,*** mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a b-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemaseproducing bacteria,revealing a new strategy to combat b-lactamase-mediated antimicrobial resistance.

关键词： Carbapenemase Metallo/serine-b-lactamase inhibitor Avibactam Meropenem Antimicrobial resistance

Proteins as nanomagnets and magnetoreceptors

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Zoological Research 2024年第4期45卷 831-832页

作者： P.J.Hore Department of Chemistry University of OxfordUK

It is an appealing notion that a protein molecule could act as a nanomagnet.A genetically encodable biomolecule with a permanent magnetic moment at room temperature could have a range of applications:a magnetogenetic actuator,a magnetic tag for purifying and immobilizing enzymes,a contrast agent for magnetic resonance imaging,and a basis for a biomimetic magnetic sensing device,to name just a few.A magnetic protein could perhaps also function as the sensor in the magnetic compass that enables small songbirds to navigate the huge distances between their breeding and wintering *** though such possibilities may be,how realistic are they?

关键词： magnetic magnets enable

Probing the Kinematic Signatures of Planet Formation in the Gas Disk of MWC 480

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Research in Astronomy and Astrophysics 2024年第6期24卷 110-118页

作者： Min Zhao Haochuan Yu Zhengxiang Li Department of Astronomy Beijing Normal UniversityBeijing 100875China Sub-department of Astrophysics Department of PhysicsUniversity of OxfordOxfordOX13RHUK

The disk around MWC 480 has shown multiple substructures in both dust and gas observations,possibly suggesting ongoing planet formation in *** this paper,we explore the gas kinematics of the MWC 480 disk by analyzing the archival Atacama Large Millimeter/submillimeter Array observations of^(12)CO(J=2-1),^(13)CO(J=2-1),and C^(18)O(J=2-1).By modeling the line-of-sight velocities,inferred from the Doppler shifts of the emission lines,we are able to decompose the three-dimensional(3D)velocity field of the disk into rotational,radial,and vertical *** analysis reveals the presence of large-scale gas flows in the(r,z)***,we identify potential meridional flows across various heights as traced by all three CO isotopologues in the 80–120 au region,possibly associated with ongoing planet formation activities in this ***,we find upward flows near 200 au for all three CO isotopologues,which may point to the presence of disk winds.

关键词： protoplanetary disks planet-disk interactions planet-star interactions

Suffocated shoots:Hypoxia-induced synthesis of salicylic acid inhibits plant regeneration

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Molecular Plant 2024年第4期17卷 528-530页

作者： Ximena Chirinos Francesco Licausi Department of Biology University of OxfordSouth Parks RoadOxford OX13RBUK

Plant cells possess the unique ability to revert differentiated somatic cells back to a pluripotent state,a trait utilized in in vitro tissue *** plant propagation strategy involves the exogenous supplementation of auxin and cytokinin,two phytohormones that promote cellular reprogramming and de novo *** exposed to an auxin-rich medium,somatic cells proliferate and form the callus,a pluripotent cell *** the attainment of pluripotency,the callus can be transferred to a cytokinin-rich medium to induce shoot regeneration.

关键词： plant synthesis transferred

Towards Domain-agnostic Depth Completion

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Machine Intelligence Research 2024年第4期21卷 652-669页

作者： Guangkai Xu Wei Yin Jianming Zhang Oliver Wang Simon Niklaus Simon Chen Jia-Wang Bian Zhejiang university Hangzhou 310058China DaJiang Technology Shenzhen 518057China Adobe Research California 95110USA university of oxford Oxford OX12JDUK

Existing depth completion methods are often targeted at a specific sparse depth type and generalize poorly across task *** present a method to complete sparse/semi-dense,noisy,and potentially low-resolution depth maps obtained by various range sensors,including those in modern mobile phones,or by multi-view reconstruction *** method leverages a data-driven prior in the form of a single image depth prediction network trained on large-scale datasets,the output of which is used as an input to our *** propose an effective training scheme where we simulate various sparsity patterns in typical task *** addition,we design two new benchmarks to evaluate the generalizability and robustness of depth completion *** simple method shows superior cross-domain generalization ability against state-of-the-art depth completion methods,introducing a practical solution to highqualitydepthcapture onamobile device.

关键词： Monocular depth estimation depth completion zero-shot generalization scene reconstruction neural network.

3D printing of poly(ethyleneimine)-functionalized Mg-Al mixed metal oxide monoliths for direct air capture of CO_(2)

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Journal of Energy Chemistry 2024年第9期96卷 491-500页

作者： Qingyang Shao Zhuozhen Gan Bingyao Ge Xuyi Liu Chunping Chen Dermot O’Hare Xuancan Zhu Research Center of Solar Power&Refrigeration School of Mechanical EngineeringShanghai Jiao Tong UniversityShanghai 200240China Chemistry Research Laboratory Department of ChemistryUniversity of OxfordOxford OX13TAUK

Direct air capture(DAC)of CO_(2)plays an indispensable role in achieving carbon-neutral goals as one of the key negative emission *** large air flows are required to capture the ultradilute CO_(2)from the air,lab-synthesized adsorbents in powder form may cause unacceptable gas pressure drops and poor heat and mass transfer efficiencies.A structured adsorbent is essential for the implementation of gas-solid contactors for cost-and energy-efficient DAC *** this study,efficient adsorbent poly(ethyleneimine)(PEI)-functionalized Mg-Al-CO_(3)layered double hydroxide(LDH)-derived mixed metal oxides(MMOs)are three-dimensional(3D)printed into monoliths for the first time with more than 90%adsorbent *** printing process has been optimized by initially printing the LDH powder into monoliths followed by calcination into MMO *** structure exhibits a 32.7%higher specific surface area and a 46.1%higher pore volume,as compared to the direct printing of the MMO powder into a *** impregnation of PEI,the monolith demonstrates a large adsorption capacity(1.82 mmol/g)and fast kinetics(0.7 mmol/g/h)using a CO_(2)feed gas at 400 ppm at 25℃,one of the highest values among the shaped DAC *** of the amino-polymers during the post-printing process affects the diffusion of CO_(2),resulting in slower adsorption kinetics of pre-impregnation monoliths compared to post-impregnation *** optimal PEI/MeOH ratio for the post-impregnation solution prevents pores clogging that would affect both adsorption capacity and kinetics.

关键词： 3D printing Mixed metal oxides Amine functionalization Structured adsorbent Direct air capture

Palliative long-term abdominal drains vs large volume paracenteses for the management of refractory ascites in end-stage liver disease

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World Journal of Hepatology 2024年第3期16卷 428-438页

作者： Senamjit Kaur Rodrigo V Motta Bryony Chapman Victoria Wharton Jane D Collier Francesca Saffioti oxford Liver Unit Department of Gastroenterology and HepatologyOxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom oxford Liver Unit and Translational Gastroenterology Unit Nuffield Department of MedicineUniversity of OxfordOxford OX39DUUnited Kingdom

BACKGROUND Long-term abdominal drains(LTAD)are a cost-effective palliative measure to manage malignant ascites in the community,but their use in patients with end-stage chronic liver disease and refractory ascites is not routine *** safety and cost-effectiveness of LTAD are currently being studied in this setting,with preliminary positive *** hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis(LVP)in patients with cirrhosis and refractory ascites and may offer advantages in patients’quality of *** To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver *** A retrospective,observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was ***’s exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables,***-Meier survival estimates were generated to stratify time-related outcomes according to the type of *** Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular *** baseline characteristics were similar between the *** antibiotics were more frequently prescribed in patients with LTAD(P=0.012),while the incidence of peritonitis did not differ between the two groups(P=0.46).The incidence of acute kidney injury(P=0.014)and ascites/drain-related hospital admissions(P=0.004)were significantly higher in the LVP *** overall survival was similar in the two groups(log-rank P=0.26),but the endpoint-free survival was significantly shorter in the LVP group(P=0.003,P<0.001,P=0.018 for first ascites/drain-related admission,acute kidney injury and drain

关键词： Decompensated liver cirrhosis Indwelling abdominal catheter Rocket drain Palliative care Safety Quality of life